Optimal single sampling time-point for monitoring of praziquantel exposure in children

Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC–MS/MS). The correlation between area under the plasma concentration–time curve from 0 to 8 h (AUC8) and plasma concentrations at each specific sampling time-point was determined by Pearson’s correlation coefficient (r2). The median age (range) of the study population was 12.5 years (10–17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC8 for both total praziquantel (r2 = 0.81, p < 0.001) and S-praziquantel (r2 = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC8 (r2 = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer.

Predictive models for chronic kidney disease after radical or partial nephrectomy in renal cell cancer using early postoperative serum creatinine levels

Background Several predictive factors for chronic kidney disease (CKD) following radical nephrectomy (RN) or partial nephrectomy (PN) have been identified. However, early postoperative laboratory values were infrequently considered as potential predictors. Therefore, this study aimed to develop predictive models for CKD 1 year after RN or PN using early postoperative laboratory values, including serum creatinine (SCr) levels, in addition to preoperative and intraoperative factors. Moreover, the optimal SCr sampling time point for the best prediction of CKD was determined. Methods Data were retrospectively collected from patients with renal cell cancer who underwent laparoscopic or robotic RN (n = 557) or PN (n = 999). Preoperative, intraoperative, and postoperative factors, including laboratory values, were incorporated during model development. We developed 8 final models using information collected at different time points (preoperative, postoperative day [POD] 0 to 5, and postoperative 1 month). Lastly, we combined all possible subsets of the developed models to generate 120 meta-models. Furthermore, we built a web application to facilitate the implementation of the model. Results The magnitude of postoperative elevation of SCr and history of CKD were the most important predictors for CKD at 1 year, followed by RN (compared to PN) and older age. Among the final models, the model using features of POD 4 showed the best performance for correctly predicting the stages of CKD at 1 year compared to other models (accuracy: 79% of POD 4 model versus 75% of POD 0 model, 76% of POD 1 model, 77% of POD 2 model, 78% of POD 3 model, 76% of POD 5 model, and 73% in postoperative 1 month model). Therefore, POD 4 may be the optimal sampling time point for postoperative SCr. A web application is hosted at https://dongy.shinyapps.io/aki_ckd. Conclusions Our predictive model, which incorporated postoperative laboratory values, especially SCr levels, in addition to preoperative and intraoperative factors, effectively predicted the occurrence of CKD 1 year after RN or PN and may be helpful for comprehensive management planning.

A practical, one-clinic visit protocol for pharmacokinetic profile generation with the ADVATE® myPKFiT® dosing tool in severe hemophilia A subjects

Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72hr washout and 5-11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE®. 39 inhibitor-negative males with SHA (FVIII:C<2%) were enrolled in a prospective sequential design PK study. Participants completed a washout, 6-sampling time point PPK protocol as well as a no-washout, reverse 2-sampling time point protocol, with samples taken during a single 3hr clinic visit 24hr-post home infusion of FVIII and then 3hr-post infusion in clinic. FVIII:C levels were analyzed by one-stage and chromogenic assays; blood group and VWF:Ag were determined; and PK parameters were analyzed using the ADVATE® myPKFiT® dosing tool. There was moderate to almost perfect agreement for the PK parameters obtained with the 2- and the 6-point PPK protocols using a one-stage FVIII:C assay and a substantial to almost perfect agreement using a chromogenic FVIII:C assay. Significant associations between specific PK parameters and blood group and VWF:Ag were observed. The no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol can be used in the routine clinical setting since it demonstrates sufficient accuracy compared to the more demanding and less practical washout, 6-sampling time point PPK protocol in persons with SHA receiving ADVATE®.

Intraindividual Variation and Personal Specificity of Salivary Microbiota

Salivary microbiota is a typical habitat of the human microbiome. This study intended to use salivary microbiota as a model aiming to systematically address the influence of collection methods and temporal dynamics on the human microbiota compared to personal specificity. We carried out a supervised short-term longitudinal study to evaluate the influence of the change of collection methods and sampling time point on salivary microbiota in 10 systemically and orally healthy individuals with certain confounding factors (sex, oral and general health state, medication history, physical exercise, diet, and oral hygiene behavior) controlled before and during the sampling period. The microbial profiles were analyzed by 16S rDNA V3 to V4 hypervariable region amplicon sequencing. The taxonomic structure represented by the dominant species and the weighted UniFrac distance algorithm were used to demonstrate the individual specificity and the intraindividual variation introduced by the change of collection method and sampling time point. The findings suggested individual specificity existed in salivary microbiota from individuals with similar oral and general health status. The intraindividual variation brought by the change of collection method or sampling time point might introduce remarkable perturbation with the personal specificity. Insights into the intraindividual variation and personal specificity of salivary microbiota will enhance our understanding in salivary microbiota-related research. We recommend keeping collection conditions consistent within a study to avoid interference brought by the sampling. The strategy of repeated sampling at multiple time points as representative samples, as well as thorough interpretation of the complex relationships and causality between microbiome composition and disease without the interference of temporal dynamics, is optimal for research exploring the relationship between the salivary microbiome and disease.

Metabonomic Investigation on Rats’ Dynamic Responses to Cantonese Herbal Tea Intake

GC-MS-based metabonomics was applied to investigate the urinary metabolic response to Cantonese Herbal tea (CHT) intake during a 38-day-period. Orthogonal projection on latent structures discriminant analysis (OPLS-DA) with student’s t-test revealed that the global characterization of metabolic changes at each sampling time point were different. Dynamic sampling made it possible to evaluate dynamic metabolic responses to CHT intake.